Complete validation of the radioimmunoassay for growth hormone and LH in the brain has been accomplished; recovery of rat pituitary hormones added to brain extracts ranged from 92-112 percent. Identical parallelism on serial dilution is seen when rat pituitary growth hormone or LH is compared with the immunoreactive counterparts extracted from the CNS. Immunoequivalent amounts of brain growth hormone or LH bind to respective antisera in a fashion identical to that of pituitary hormones. Classical bioassay in the 21-day post-hypophysectomized animal has shown that brain extracts significantly promote growth of the tibial epiphyseal cartilage, and restore weight and normal histology of the thyroid, adrenal, ovaries and testes. We have secured data to suggest that hypothalamically derived LH is probably the short-loop negative feedback mechanism stimulating the proestrous pituitary LH surge, a hypothesis that will require further testing. We have also quantitated a most remarkable preparturitional rise in these pituitary-like peptides, an observation comparable in magnitude to what has been described for neuronal proliferation, DNA, and estrogen receptors of fetal brain at the time of birth. Future studies will continue to focus on descriptive mapping of these phenomena in the rat brain. New approaches will seek to provide evidence that these particular peptides are synthesized in brain cells; fluorescent immunocytochemistry will be more thoroughly applied; we will examine whether receptors for these peptides exist on brain cells grown in tissue culture and from autoradiography of brain slices incubated with labelled hormones and with labelled antisera to specific peptides; we will examine the influence of gonadal steroids on hypothalamic LH and attempt to correlate changes with alterations in estrogen and progestin receptors in the hypothalamus; and we will measure alterations in brain pituitary-like peptides against known physiologic determinants such as fetal development, birth, neonatal growth, puberty, pregnancy and aging. We will also clarify whether the growth-promoting effects of brain extracts on thyroid, adrenal, and gonadal growth, in hypophysectomized rats, are entirely due to immunoassayable pituitary-like peptides.